Bupropion hydrochloride is a common chloropropiophenone antidepressant, most recently found useful for helping patients stop smoking. See PCT Application No. WO 99/38,499. Novel methods of making bupropion hydrochloride include those taught by Mehta. See U.S. Pat. Nos. 3,819,706 and 3,885,046. Relative to conventional antidepressants, bupropion hydrochloride has no significant sympathomimetic, sympatholytic, anticholinergic or cardiovascular effects. Bupropion hydrochloride is sold in immediate release, modified release and extended release tablet forms. Regardless of its form, stability of bupropion hydrochloride is affected by a number of factors including formulation microenvironments and storage conditions.
Various bupropion hydrochloride formulations have been proposed in the art, designed to increase its stability. For example, one group reports that degradation can be inhibited or prevented by including in the formulation stabilizers such as L-cysteine hydrochloride, glycine hydrochloride, malic acid, sodium metabisulfite, citric acid, tartaric acid and L-cystine dihydrochloride. See U.S. Pat. Nos. 5,358,970 and 5,763,493. The same group also reports that degradation of bupropion hydrochloride can be inhibited by use of stabilizers including ascorbic acid or isoascorbic acid. See U.S. Pat. Nos. 5,541,231 and 5,731,000. Another group has reported that the drug can be stabilized by formulating it with inorganic acids such as hydrochloric acid, phosphoric acid, nitric acid and sulfuric acid or combinations thereof. See U.S. Pat. No. 5,968,553 and PCT Application No. WO 99/33,456. Still others have reported that substances such as fumaric acid can inhibit degradation of bupropion hydrochloride. See PCT Application No. WO 99/33,457.
This invention is directed to pharmaceutical formulations of bupropion hydrochloride (as the drug or active ingredient), in which the stability of the bupropion hydrochloride is augmented by the addition of a pharmaceutically acceptable stabilizer in an amount effective to increase stability.